A Novel Mutation Eliminates GATA-1 and RUNX1-Mediated Promoter Activity in Galactosyltransferase Gene

INTRODUCTION: Mutations in the promoter region and exons of ABO gene may cause changes in the expression of blood group antigens, often showing a weak ABO phenotype. Here, we identified a novel weak ABO subgroup allele that caused B_el phenotype and explored its mechanisms. METHODS: The ABO phenotype of subjects (Chinese Han nationality) was classified by serological method. The plasma activity of erythrocyte glycosyltransferase was detected by the phosphate coupling method. ABO subtype genotyping was performed by PCR-SSP and exon sequencing. The activity of the promoter was evaluated by a dual-luciferase reporter assay. RESULTS: We identified a mutation exon 1 c.15_16insTGTTG of the B allele in a B_el subject. Genealogical investigation showed that the mutation was inherited from her mother. The mutation was located in the promoter region of the ABO gene. The dual-luciferase reporter assay showed that the mutation inactivated GATA-1 and RUNX1-mediated activity of the ABO gene promoter, leading to a decrease in the expression and activity of B glycosyltransferase. CONCLUSION: A novel B_var ABO subgroup allele was identified. The novel mutation can reduce the promoter activity that activated by GATA-1 and RUNX1, subsequently causing the B_el phenotype.